Opdivo is the first and only Immuno-Oncology
treatment proven in a Phase 3 trial to significantly extend overall
survival for patients with recurrent or metastatic squamous cell
head and neck cancer who had been previously treated with
platinum-based therapy1
NCCN guidelines recently updated to include
treatment with Opdivo as the only category 1 single-agent therapy
for certain patients in this setting2
Opdivo has now been approved in five tumor
types in under two years1
Bristol-Myers Squibb Company (NYSE:BMY) announced today that the
U.S. Food and Drug Administration (FDA) has approved Opdivo
(nivolumab) injection, for intravenous use, for the treatment of
patients with recurrent or metastatic squamous cell carcinoma of
the head and neck (SCCHN) with disease progression on or after
platinum-based therapy.1 Opdivo is the first and only
Immuno-Oncology treatment proven in a Phase 3 trial to
significantly extend overall survival (OS) for these patients.1 In
oncology clinical trials, OS is considered the gold standard
primary endpoint to evaluate the outcome of any therapy.3
The approval was based on results from the Phase 3, CheckMate
-141 trial in which Opdivo demonstrated statistically
significant and clinically meaningful superior OS vs the comparator
arm (investigator’s choice of methotrexate, docetaxel or
cetuximab), with a 30% reduction in the risk of death (HR=0.70 [95%
CI: 0.53-0.92; p=0.0101]).1 The median OS was 7.5 months (95% CI:
5.5-9.1) for Opdivo compared to 5.1 months (95% CI: 4.0-6.0) for
investigator’s choice.1 Opdivo is associated with immune-mediated:
pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and
renal dysfunction, skin adverse reactions, encephalitis, other
adverse reactions; infusion reactions; and embryo-fetal toxicity.
Please see the Important Safety Information section below.
“With this approval in head and neck cancer, we continue to lead
the field in bringing our Immuno-Oncology science and the potential
for increasing survival to more people with cancer,” said Chris
Boerner, Head of U.S. Commercial, Bristol-Myers Squibb. “We take
tremendous pride in the unprecedented speed and rigor with which we
have brought Opdivo to market to address unmet needs across more
tumor types than any other Immuno-Oncology treatment.”
Squamous cell carcinoma of the head and neck (SCCHN) accounts
for more than 90% of all head and neck cancers, and more than 50%
of SCCHN patients present with Stage III or higher disease (locally
advanced or metastatic), which has higher potential for progression
and recurrence.4,5 The relative five-year survival rate for
metastatic head and neck cancers is <38%, and can be as low as
4% for recurrent or metastatic Stage IV disease.6,7
“Squamous cell carcinoma of the head and neck that progresses on
or after platinum-based therapy is a debilitating and hard-to-treat
disease associated with a very poor prognosis,” said Maura
Gillison, M.D., Ph.D., lead investigator, Jeg Coughlin Chair of
Cancer Research, The Ohio State University Wexner Medical Center.
“This latest approval for Opdivo reinforces the potential to
provide patients with improved overall survival, considered the
gold standard in cancer care.”
Based on a pre-planned interim analysis, CheckMate -141 was
stopped early in January 2016 because an assessment conducted by
the independent Data Monitoring Committee concluded the study met
its primary endpoint of OS. In April 2016, the FDA granted
Breakthrough Therapy Designation to Opdivo for recurrent or
metastatic SCCHN after platinum-based therapy, underscoring the
need for new treatment approaches for this disease. In October, the
U.S. National Comprehensive Cancer Network (NCCN) updated its
clinical practice guidelines to recommend treatment with Opdivo as
the only category 1 single-agent therapy for patients with
recurrent or metastatic head and neck cancer with disease
progression on or after platinum-containing chemotherapy.2 Opdivo
has now been approved in five tumor types in under two years.1
CheckMate -141 Confirms Superior OS in
SCCHN
CheckMate -141 was a global Phase 3, open-label, randomized,
trial evaluating Opdivo versus investigator’s choice of therapy in
patients with recurrent or metastatic SCCHN who had tumor
progression during or within six months of receiving platinum-based
therapy administered in the adjuvant, neo-adjuvant, primary
(unresectable locally advanced) or metastatic setting.1,8 Patients
were included regardless of their HPV or PD-L1 status.1 Patients
were randomized 2:1 to receive Opdivo 3 mg/kg intravenously over 60
minutes every two weeks (n=240), or investigator’s choice (n=121)
of: methotrextate 40 to 60 mg/m2 intravenously weekly, docetaxel 30
to 40 mg/m2 intravenously weekly, or cetuximab 400 mg/m2
intravenously once then 250 mg/m2 weekly.1 Therapies chosen for
investigator’s choice represent the most commonly used therapies in
the platinum refractory setting.9,10 The primary endpoint was OS.1
The trial’s secondary endpoints included progression-free survival
(PFS) and objective response rate (ORR).11
In the trial, Opdivo demonstrated statistically significant
superior OS with a 30% reduction in the risk of death (HR=0.70 [95%
CI: 0.53-0.92; p=0.0101]), and a median OS of 7.5 months (95% CI:
5.5-9.1) for Opdivo compared to 5.1 months (95% CI: 4.0-6.0) for
the investigator’s choice arm.1 There were no statistically
significant differences between the two arms for PFS (HR=0.89; 95%
CI: 0.70, 1.13) or ORR (13.3% [95% CI: 9.3, 18.3] vs 5.8% [95% CI:
2.4, 11.6] for Opdivo and investigator’s choice, respectively.1
Data from CheckMate -141 were published in The New England Journal
of Medicine in October.8
“We are excited to see the continued benefits of ongoing
Immuno-Oncology research from a company with a long-standing
commitment to head and neck cancer
like Bristol-Myers Squibb,” said Brian Hill, oral cancer
survivor and founder, The Oral Cancer Foundation. “Today’s approval
provides hope for the thousands of previously treated SCCHN
patients and their loved ones by bringing a new treatment option
that has the potential to extend lives.”
The safety profile of Opdivo in CheckMate -141 was
consistent with prior studies in patients with melanoma and
non-small cell lung cancer.8 Opdivo was discontinued in 14% of
patients and was delayed in 24% of patients for an adverse
reaction.1 Serious adverse reactions occurred in 49% of patients
receiving Opdivo.1 The most frequent serious adverse reactions
reported in at least 2% of patients receiving Opdivo were
pneumonia, dyspnea, aspiration pneumonia, respiratory failure,
respiratory tract infection, and sepsis.1 Please see the Important
Safety Information section below.
About Head & Neck
Cancer
Cancers that are known as head and neck cancers usually begin in
the squamous cells that line the moist mucosal surfaces inside the
head and neck, such as inside the mouth and the throat.12 In 2016,
approximately 64,000 new cases of head and neck cancer are
estimated to be diagnosed in the U.S., resulting in more than
13,000 deaths.4,13,14 Head and neck cancers are more than twice as
common among men as they are among women.4
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of
cancer care that is focused on Immuno-Oncology, now considered a
major treatment modality alongside surgery, radiation and
chemotherapy for certain types of cancer.
We have a comprehensive clinical portfolio of investigational
and approved Immuno-Oncology agents, many of which were discovered
and developed by our scientists. We pioneered the research leading
to the first regulatory approval for the combination of two
Immuno-Oncology agents and continue to study the role of
combinations in cancer.
Our collaboration with academia as well as small and large
biotech companies is responsible for researching the potential
Immuno-Oncology and non-Immuno-Oncology combinations, with the goal
of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing
expectations in hard-to-treat cancers and the way patients live
with cancer.
U.S. FDA APPROVED INDICATIONS FOR
OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with metastatic non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and post-transplantation brentuximab vedotin. This
indication is approved under accelerated approval based on overall
response rate. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
IMPORTANT SAFETY
INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have
been reported. Monitor patients for signs with radiographic imaging
and for symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or more severe pneumonitis. Permanently discontinue for
Grade 3 or 4 and withhold until resolution for Grade 2. In patients
receiving OPDIVO monotherapy, fatal cases of immune-mediated
pneumonitis have occurred. Immune-mediated pneumonitis occurred in
3.1% (61/1994) of patients. In patients receiving OPDIVO with
YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of
patients.
In Checkmate 205 and 039, pneumonitis, including interstitial
lung disease, occurred in 4.9% (13/263) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO
monotherapy for Grade 2 or 3 and permanently discontinue for Grade
4 or recurrent colitis upon re-initiation of OPDIVO. When
administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2
and permanently discontinue for Grade 3 or 4 or recurrent colitis.
In patients receiving OPDIVO monotherapy, immune-mediated colitis
occurred in 2.9% (58/1994) of patients. In patients receiving
OPDIVO with YERVOY, immune-mediated colitis occurred in 26%
(107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 immune-mediated hepatitis. In patients receiving
OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8%
(35/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated hepatitis occurred in 13% (51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated
adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer hormone replacement as clinically
indicated and corticosteroids for Grade 2 or greater hypophysitis.
Withhold for Grade 2 or 3 and permanently discontinue for Grade 4
hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal
insufficiency. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement
therapy for hypothyroidism. Initiate medical management for control
of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients. In patients receiving OPDIVO with
YERVOY, hypophysitis occurred in 9% (36/407) of patients. In
patients receiving OPDIVO monotherapy, adrenal insufficiency
occurred in 1% (20/1994) of patients. In patients receiving OPDIVO
with YERVOY, adrenal insufficiency occurred in 5% (21/407) of
patients. In patients receiving OPDIVO monotherapy, hypothyroidism
or thyroiditis resulting in hypothyroidism occurred in 9%
(171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994)
of patients receiving OPDIVO monotherapy. In patients receiving
OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (89/407) of patients.
Hyperthyroidism occurred in 8% (34/407) of patients receiving
OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy,
diabetes occurred in 0.9% (17/1994) of patients. In patients
receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of
patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased
serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In patients
receiving OPDIVO monotherapy, immune-mediated nephritis and renal
dysfunction occurred in 1.2% (23/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated nephritis and renal
dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4
rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and
refer the patient for specialized care for assessment and
treatment; if confirmed, permanently discontinue. In patients
receiving OPDIVO monotherapy, immune-mediated rash occurred in 9%
(171/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of
patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar
puncture. Withhold OPDIVO in patients with new-onset moderate to
severe neurologic signs or symptoms and evaluate to rule out other
causes. If other etiologies are ruled out, administer
corticosteroids and permanently discontinue OPDIVO for
immune-mediated encephalitis. In patients receiving OPDIVO
monotherapy, encephalitis occurred in 0.2% (3/1994) of patients.
Fatal limbic encephalitis occurred in one patient after 7.2 months
of exposure despite discontinuation of OPDIVO and administration of
corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO the following clinically
significant immune-mediated adverse reactions occurred in <1.0%
of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial
and abducens nerve paresis, demyelination, polymyalgia rheumatica,
autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis,
sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor
dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been
reported in <1.0% of patients in clinical trials. Discontinue
OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt
or slow the rate of infusion in patients with Grade 1 or 2. In
patients receiving OPDIVO monotherapy, infusion-related reactions
occurred in 6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred in 2.5%
(10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who
received allogeneic HSCT after OPDIVO. Outcomes were evaluated in
17 patients from Checkmate 205 and 039, who underwent allogeneic
HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning). Thirty-five
percent (6/17) of patients died from complications of allogeneic
HSCT after OPDIVO. Five deaths occurred in the setting of severe or
refractory GVHD. Grade 3 or higher acute GVHD was reported in 29%
(5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of
patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients.
Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic
encephalitis without an identified infectious cause, and Grade 3
(n=1) suspected viral encephalitis. Hepatic veno-occlusive disease
(VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ
failure. Other cases of hepatic VOD after reduced-intensity
conditioned allogeneic HSCT have also been reported in patients
with lymphoma who received a PD-1 receptor blocking antibody before
transplantation. Cases of fatal hyperacute GVHD have also been
reported. These complications may occur despite intervening therapy
between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to 4) acute
GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause
fetal harm when administered to a pregnant woman. Advise pregnant
women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during
treatment with an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human
milk. Because many drugs, including antibodies, are excreted in
human milk and because of the potential for serious adverse
reactions in nursing infants from an OPDIVO-containing regimen,
advise women to discontinue breastfeeding during treatment. Advise
women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions
occurred in 42% of patients receiving OPDIVO . The most frequent
Grade 3 and 4 adverse drug reactions reported in 2% to <5% of
patients receiving OPDIVO were abdominal pain, hyponatremia,
increased aspartate aminotransferase, and increased lipase. In
Checkmate 066, serious adverse reactions occurred in 36% of
patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions
occurred in 41% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse reactions reported in ≥2% of patients
receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and
diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73%
and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).
The most frequent (≥10%) serious adverse reactions in the OPDIVO
plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea
(13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%).
In Checkmate 017 and 057, serious adverse reactions occurred in 46%
of patients receiving OPDIVO (n=418). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia,
pleural effusion, pneumonitis, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO (n=406). The most frequent serious
adverse reactions reported in ≥2% of patients were acute kidney
injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia.
In Checkmate 205 and 039, among all patients (safety population
[n=263]), adverse reactions leading to discontinuation (4.2%) or to
dosing delays (23%) occurred. The most frequent serious adverse
reactions reported in ≥1% of patients were infusion-related
reaction, pneumonia, pleural effusion, pyrexia, rash and
pneumonitis. Ten patients died from causes other than disease
progression, including 6 who died from complications of allogeneic
HSCT. Serious adverse reactions occurred in 21% of patients in the
safety population (n=263) and 27% of patients in the subset of
patients evaluated for efficacy (efficacy population [n=95]). In
Checkmate 141, serious adverse reactions occurred in 49% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in at least 2% of patients receiving OPDIVO were
pneumonia, dyspnea, respiratory failure, respiratory tract
infections, and sepsis.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206)
vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In
Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%),
diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and
dyspnea (20%). The most common (≥20%) adverse reactions in the
OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%),
and nausea (28%). In Checkmate 017 and 057, the most common adverse
reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue,
musculoskeletal pain, cough, dyspnea, and decreased appetite. In
Checkmate 025, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=406) vs everolimus (n=397) were
asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28%
vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs
32%), constipation (23% vs 18%), decreased appetite (23% vs 30%),
back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate
205 and 039, among all patients (safety population [n=263]) and the
subset of patients in the efficacy population (n=95), respectively,
the most common adverse reactions (≥20%) were fatigue (32% and
43%), upper respiratory tract infection (28% and 48%), pyrexia (24%
and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the
subset of patients in the efficacy population (n=95), the most
common adverse reactions also included rash (31%), musculoskeletal
pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and
peripheral neuropathy (21%). In Checkmate 141, the most common
adverse reactions (≥10%) in patients receiving OPDIVO were cough
and dyspnea at a higher incidence than investigator’s choice.
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common
adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations
Checkmate 067 - advanced melanoma alone or in combination
with YERVOY; Checkmate 037 and 066 - advanced melanoma;
Checkmate 017 - squamous non-small cell lung cancer (NSCLC);
Checkmate 057 - non-squamous NSCLC; Checkmate 025 -
renal cell carcinoma; Checkmate 205/039 - classical Hodgkin
lymphoma; Checkmate 141 – squamous cell carcinoma of the
head and neck.
Please see U.S. Full Prescribing Information for OPDIVO and
YERVOY, including Boxed WARNING regarding immune-mediated
adverse reactions for YERVOY.
About the Opdivo Clinical Development
Program
Bristol-Myers Squibb has a broad, global development program to
study Opdivo in multiple tumor types consisting of more than 50
trials – as monotherapy or in combination with other therapies – in
which more than 8,000 patients have been enrolled worldwide.
About Bristol-Myers Squibb’s Patient
Support Programs for Opdivo
Bristol-Myers Squibb remains committed to helping patients
through treatment with Opdivo. For support and assistance,
patients and physicians may call 1-855-OPDIVO-1. This number offers
a one-stop access to a range of support services for patients and
healthcare professionals alike.
About Bristol-Myers Squibb’s Access
Support
Bristol-Myers Squibb is committed to helping patients
access Opdivo and offers BMS Access Support® to
support patients and providers in gaining access. BMS Access
Support, the Bristol-Myers Squibb Reimbursement Services
program, is designed to support access to BMS medicines and
expedite time to therapy through reimbursement support including
Benefit Investigations, Prior Authorization Facilitation, Appeals
Assistance, and assistance for patient out-of-pocket costs. BMS
Access Support assists patients and providers throughout the
treatment journey – whether it is at initial diagnosis or in
support of transition from a clinical trial. More information about
our reimbursement support services can be obtained by calling
1-800-861-0048 or by visiting www.bmsaccesssupport.com. For
healthcare providers seeking specific reimbursement information,
please visit the BMS Access Support Product section by visiting
www.bmsaccesssupportopdivo.com.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial
rights to develop and commercialize Opdivo globally except in
Japan, South Korea and Taiwan, where Ono had retained all rights to
the compound at the time. On July 2014, Ono and Bristol-Myers
Squibb further expanded the companies’ strategic collaboration
agreement to jointly develop and commercialize multiple
immunotherapies – as single agents and combination regimens – for
patients with cancer in Japan, South Korea and Taiwan.
About Bristol-Myers
Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol-Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Forward-looking statements in this press release
should be evaluated together with the many uncertainties that
affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2015 in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
References
1. Opdivo Prescribing Information. Opdivo U.S. Product
Information. Last updated: November 10, 2016. Princeton, NJ:
Bristol-Myers Squibb Company. 2. National Comprehensive Cancer
Network Clinical Practice Guidelines in Oncology. Head and Neck
Cancers. October 11, 2016. 3. Driscoll JJ, et al. Overall survival:
still the gold standard: why overall survival remains the
definitive end point in cancer clinical trials. Cancer J. 2009;
15(5):401-5. 4.
American Cancer Society. Oral Cavity and
Oropharyngeal Cancer.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003128-pdf.pdf
Updated January 27, 2016. Accessed June 24, 2016. 5. Decision
Resources. SCCHN. September 2012. 6.
National Cancer Institute. “SEER Stat Fact
Sheets: Oral Cavity and Pharynx Cancer.” Available at:
http://seer.cancer.gov/statfacts/html/oralcav.html.
7. Argiris, Athanassios, Arlene Forastiere. American Cancer
Society. “Prognostic Factors and Long-Term Survivorship in Patients
with Recurrent or Metastatic Carcinoma of the Head and Neck.”
Updated September 27, 2004. 8. Ferris RL, Blumenschein G, Fayette
J, et al. Nivolumab for recurrent squamous-cell carcinoma of the
head and neck. N Engl J Med. 2016: DOI:10.1056/NEJMoa1602252. 9.
IPSOS Oncology Monitor, MAT May 2016 Projected Annual Treatments
10. IMS Health APLD, MAT June 2016 Projected Annual Treated Patient
Counts 11.
Clinicaltrials.gov. “Trial of Nivolumab vs
Therapy of Investigator's Choice in Recurrent or Metastatic Head
and Neck Carcinoma (CheckMate 141).” Available at:
https://clinicaltrials.gov/ct2/show/NCT02105636?term=checkmate+141&rank=1
12. National Cancer Institute. “Head and Neck Cancers.”
http://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet.
Accessed on June 24, 2016. 13.
American Cancer Society. Laryngeal and
Hypopharyngeal Cancers.
http://www.cancer.org/cancer/laryngealandhypopharyngealcancer/detailedguide/laryngeal-and-hypopharyngeal-cancer-key-statistics.
Updated February 17, 2016. Accessed July 26, 2016.
14.
American Cancer Society. Nasal Cavity and
Paranasal Sinus Cancers.
http://www.cancer.org/cancer/nasalcavityandparanasalsinuscancer/detailedguide/nasal-cavity-and-paranasal-sinuses-cancer-key-statistics.
Updated March 2, 2015. Accessed July 26, 2016.
OPDIVO, YERVOY and Access Support are trademarks of
Bristol-Myers Squibb Company. Other brands listed are the
trademarks of their respective owners.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161110006616/en/
Bristol-Myers Squibb CompanyMedia Inquiries:Carrie
Fernandez,
609-897-4957carrie.fernandez@bms.comorInvestors:Tim Power,
609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
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